FDA 510(k) Search - By Innolitics (SaMD and AI Experts)

AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview

Intended Use

The Hevylite IgG Kappa kit is a quantitative in vitro assay intended for the measurement of IgG Kappa (IgG heavy chain and Kappa light chain intact immunoglobulin) in serum using the Optilite analyser. Measurement of Hevylite IgG Kappa is used alongside Hevylite IgG Lambda to calculate the IgG Lambda ratio. The Hevylite IgG Kappa / IgG Lambda ratio can be used when monitoring previously diagnosed IgG multiple myeloma patients and is used in conjunction with other laboratory tests and clinical evaluations. The assignment of complete response is reliant upon other tests including immunofixation, bone marrow and urine assessments.

The Hevylite IgG Lambda kit is a quantitative in vitro assay intended for the measurement of IgG heavy chain and Lambda light chain intact immunoglobulin) in serum using Site Optilite analyser. Measurement of Hevylite IgG Lambda is used alongside Hevylite IgG Kappa to calculate the IgG Kappa / IgG Lambda ratio. The Hevylite IgG Kappa / IgG Lambda ratio can be used when monitoring previously diagnosed IgG multiple myeloma patients and is used in conjunction with other laboratory tests and clinical evaluations. The assignment of complete response is reliant upon other tests including immunofixation, bone marrow and urine assessments.

Device Description

The Hevylite Human IgG Kappa and IgG Lambda Kits contain vials of ready-to-use polyclonal monospecific sheep anti-lgG antisera against combined γ heavy and κ light chain or combined y heavy and À light chain, calibrators (six levels), controls (low and high) and reaction buffer in liquid form. The reagents contain 0.099% sodium azide as preservative.

AI/ML Overview

The provided text describes the performance characteristics of the Optilite Hevylite IgG Kappa Kit and Optilite Hevylite IgG Lambda Kit, which are in vitro diagnostics. It does not describe an AI medical device, but rather a laboratory assay. Therefore, many of the requested points, such as "multi reader multi case (MRMC) comparative effectiveness study," "standalone (i.e. algorithm only without human-in-the-loop performance)," and information on experts for ground truth and adjudication methods, are not applicable to this type of device.

However, I can extract and present the relevant information regarding the performance study of this In Vitro Diagnostic (IVD) assay.

Device Information:

Trade/Device Name: Optilite Hevylite IgG Kappa Kit, Optilite Hevylite IgG Lambda Kit
Regulation Number: 21 CFR 866.5510
Regulation Name: Immunoglobulins A, G, M, D, and E immunological test system
Regulatory Class: Class II
Product Code: PCN, PCO
Intended Use: Quantitative in vitro assay for the measurement of IgG Kappa (IgG heavy chain and kappa light chain intact immunoglobulin) and IgG Lambda (IgG heavy chain and lambda light chain intact immunoglobulin) in serum. Used alongside each other to calculate the IgG Kappa/IgG Lambda ratio, which can be used when monitoring previously diagnosed IgG multiple myeloma patients in conjunction with other laboratory tests and clinical evaluations.

Study Proving Device Meets Acceptance Criteria:

The study evaluated the analytical and clinical performance of the device by comparing it to a legally marketed predicate device (Hevylite Human IgG Kappa Kit and Hevylite Human IgG Lambda Kit for use on the Siemens BN™II, K132555).

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly list pre-defined "acceptance criteria" in a table format with pass/fail values. Instead, it presents the results of several performance studies which, taken together, demonstrate the device's suitability for its intended use and its substantial equivalence to the predicate device. The performance is demonstrated through precision, linearity, stability, detection limits, analytical specificity (interference and cross-reactivity), and method comparison studies. Clinical validity is supported by a monitoring response category comparison and data modeling.

Here's a summary of the performance metrics reported:

Performance Metric	Acceptance Criteria (Implied)	Reported Device Performance
Precision (Total %CV)	Acceptable coefficients of variation for different concentration levels.	IgGL Precision Studies:
Sample 1 (4.260): 7.6%
Sample 2 (3.148*): 5.4%
Sample 3 (5.601*): 7.7%
Sample 4 (7.621): 6.8%
Sample 5 (13.574): 7.2%
Sample 6 (16.824): 6.7%

IgGK Precision Studies:
Sample 1 (2.894): 9.0%
Sample 2 (1.313*): 6.2%
Sample 3 (2.379*): 4.2%
Sample 4 (4.262): 7.5%
Sample 5 (6.657): 5.3%
Sample 6 (13.941): 4.0% |
| Linearity/Reportable Range | Linear over the standard measuring ranges with acceptable deviation from linearity. | IgGK: Linear over 1.930 - 33.427 g/L (at 1+19 dilution) with deviation from linearity ≤ 10%.
IgGL: Linear over 1.380 - 19.300 g/L (at 1+19 dilution) with deviation from linearity ≤ 10%. (Standard measuring ranges: IgGK: 2.3 – 30.0 g/L, IgGL: 1.5 – 17.5 g/L). |
| Open Vial Stability | Maintain performance for specified duration. | Supports a claim of 3 months at 2-8°C. |
| On-Board Stability | Maintain performance for specified duration when on the instrument. | Supports a claim of 28 days (provided power is left switched on). |
| Detection Limits (LoD, LoQ) | Low enough for clinical utility. | IgG Kappa: LoB=0.000 g/L, LoD=0.009 g/L, LoQ=0.115 g/L
IgG Lambda: LoB=0.000 g/L, LoD=0.005 g/L, LoQ=0.075 g/L |
| Analytical Specificity (Interference) | Interference should be within an acceptable range (e.g., ±10% deviation). | No significant assay interference effects observed with bilirubin (200mg/L), hemoglobin (5g/L), triglyceride (1000mg/dL), intralipid (125mg/dL), or 16 commonly used drugs at specified concentrations. |
| Antigen Excess Detection | Ability to detect antigen excess to prevent false low results. | No antigen excess observed up to 100.5 g/L for IgG Kappa and 102.5 g/L for IgG Lambda (concentrations above respective standard measuring ranges). |
| Method Comparison (Correlation with Predicate) | Strong correlation coefficient (r) and acceptable Passing Bablok regression equation parameters. | IgG Kappa: 284 serum samples (range 0.2 - 47.69 g/L). y = 1.10x - 0.68 g/L; r = 0.957 (y = Optilite, x = predicate analyser).
IgG Lambda: 172 serum samples (range 0.09 - 40.65 g/L). y = 0.95x + 0.00 g/L; r = 0.823 (y = Optilite, x = predicate analyser).
IgG Kappa/Lambda Ratio: 143 serum samples (range 0.01 - 277.50 g/L). y = 1.12x - 0.17; r = 0.901 (y = Optilite, x = predicate analyser). |
| Clinical Monitoring Response Category Agreement | High kappa/weighted kappa statistics indicating good agreement between device and predicate for classifying patient responses (CR, VGPR, PR, SD, PD). | Optilite Monitoring Study (69 samples): Kappa (95% CIs) = 0.79 (0.62 – 0.96); Weighted Kappa (95% CIs) = 0.87 (0.74 – 0.98). (For 43 response classifications out of 69 monitoring samples).
Data Modelling (Transformed Data Response - H/L, 437 evaluations):* Kappa (95% CIs) = 0.75 (0.70 – 0.80); Weighted Kappa (95% CIs) = 0.86 (0.82 – 0.89).
Data Modelling (Transformed Data Response - L/H, 437 evaluations):** Kappa (95% CIs) = 0.81 (0.76 - 0.85); Weighted Kappa (95% CIs) = 0.90 (0.86 - 0.93). |
| Reference Intervals | Verification of transferred reference intervals. | Verified by testing 50 adult donor samples. IgG kappa (g/L): 4.03 – 9.78 g/L; IgG lambda (g/L): 1.97 - 5.71 g/L; IgG kappa/ IgG lambda ratio: 0.98 - 2.75. |

2. Sample Sizes Used for the Test Set and Data Provenance

Precision/Reproducibility: Six serum samples (contents not detailed, likely pooled or commercial controls/spiked samples) tested over 21 days with two runs per day on three different reagent lots on three analyzers.
Linearity: Serum samples (quantity not explicitly stated, but "serially diluted serum samples") to cover the standard measuring ranges.
Open-vial stability: Three lots of kits.
On-board stability: Three lots of kits.
Detection limit: Analyte depleted samples (60 determinations for LoB), 5 independent samples diluted with analyte depleted serum for LoQ (tested twelve times over five days).
Analytical specificity (Interference): Three serum samples with different IgG Kappa/Lambda concentrations, spiked with interfering substances.
Antigen Excess Detection: 8 monoclonal IgG Kappa and 6 monoclonal IgG Lambda samples.
Method Comparison (with predicate device):
- IgG Kappa: 284 serum samples (including 135 IgG Kappa paraprotein, 60 IgG Lambda paraprotein, 60 donor samples, and 29 other samples).
- IgG Lambda: 172 serum samples (including 42 IgG Kappa paraprotein, 59 IgG Lambda paraprotein, 59 donor samples, and 1 AL Amyloidosis sample).
- IgG Kappa/Lambda Ratio: 143 serum samples (including 39 IgG Kappa paraprotein, 44 IgG Lambda paraprotein, 59 donor samples, and 1 AL Amyloidosis sample).
Clinical Monitoring Response Category Study: 69 monitoring samples from 10 IgG Kappa patients and 12 IgG Lambda patients. The data provenance is implied to be from patient samples, consistent with clinical monitoring. Country of origin not specified, but typically for submissions to the US FDA, data from well-regulated regions (e.g., US, EU) are accepted. It is a retrospective analysis utilizing existing patient data.
Data Modelling: Monitoring sample results from the original BNII submission (predicate device's clinical data). The total number of evaluations was 437. This is a retrospective application of new data to existing clinical outcomes.
Expected values/Reference range: 50 adult donor samples.

Data Provenance: The document does not explicitly state the country of origin for the clinical samples. The studies are based on patient and donor serum samples. The clinical monitoring study and data modeling are retrospective analyses of previously collected patient data.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

This device is an IVD assay, not an AI image analysis device. Therefore, the concept of "experts establishing ground truth for a test set" in the context of image annotation is not directly applicable.

For IVDs, "ground truth" for clinical effectiveness is typically established by:

Reference Methods: Comparison against an established, validated method (the predicate device in this case, the Siemens BN™II).
Clinical Diagnosis/Outcomes: In the context of monitoring multiple myeloma, the "ground truth" for patient response categories (CR, VGPR, PR, SD, PD, Relapse from CR) is defined by clinical guidelines (NCCN Guidelines v1.2011) that integrate multiple clinical tests (immunofixation, bone marrow, urine assessments) and patient history, rather than a single expert adjudication on an image. The study compares the calculated HLC ratio response classification from the new device with that from the predicate based on these clinical definitions.

4. Adjudication Method for the Test Set

Not applicable as this is an IVD assay. The performance is assessed against analytical standards and agreement with a predicate device and established clinical guidelines for patient response classification.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done

Not applicable as this is an IVD assay, not an AI-assisted diagnostic tool involving human readers of images.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

This concept is tailored for AI devices. For this IVD, the "standalone performance" is represented by its analytical performance characteristics (precision, linearity, detection limits, specificity) and its ability to classify patient responses independently using its measured values and interpretation rules, which are then compared to the predicate device's classifications. The device itself (the Optilite analyzer and the kits) provides quantitative measurements.

7. The Type of Ground Truth Used

Analytical Performance: The ground truth for analytical performance (e.g., true concentration for linearity, known interferences for specificity) would typically be established by highly accurate reference methods or certified reference materials.
Clinical Monitoring Response: The ground truth for "clinical response categorization" (e.g., Complete Response, Partial Response) is defined by established clinical guidelines (NCCN Guidelines v1.2011) that consider a combination of laboratory tests (including immunofixation, bone marrow, and urine assessments) rather than a single, independent "ground truth" measure. The study aimed to show agreement between the new device's HLC ratio-based classification and the predicate device's HLC ratio-based classification within these established clinical guidelines.

8. The Sample Size for the Training Set

This document describes a pre-market notification (510(k)) for a medical device that is an in vitro diagnostic quantitative assay. It is not an AI/Machine Learning device that requires a "training set" in the conventional sense for model development. The "training" for such an IVD would be the development and optimization of the assay reagents and analytical procedure by the manufacturer. The data described here are for validation and verification, not for training a machine learning model.

9. How the Ground Truth for the Training Set Was Established

As noted above, there is no "training set" in the context of machine learning for this type of IVD. The development of the assay's performance characteristics (e.g., reagent formulation, calibration curve fitting) would be based on internal development work and validated against established laboratory practices and reference materials.